It is known that one of the causes of hypertentions, and coronary or cerebral circulatory diseases, which constitute the severe social problems as adult diseases, is the abnormal construction of smooth muscles and the construction of smooth muscles is caused by increasing the intracellular concentrations of calcium ion. The rise of the intracellular concentrations of calcium ion is caused (1) through the membrane potential-dependent calcium channel, (2) by releasing from the intracellular organella for storage of calcium and (3) through the receptor-dependent channel and so on, and therefore its origin is uneven. Further, it is recognized that the excessive calcium ions induce twitches of the coronary artery and the cerebrovascular and these vascular twitches constitute one of the causes of myocardial infarction, angina pectoris and cerebral infarction.
Then the calcium antagonists have been recently used for the treatment of hypertension, or coronary and cerebral circulatory diseases. However, while the calcium antagonists show antagonistic activity against the membrane potential-dependent calcium channel, scarcely show antagonistic activities against other influx of calcium ion into the cell and liberating calcium ion from the storage organella.
Whereas, in Japanese patent application Unexamined Publication (Kokai) No. 54/1987, there are disclosed N-(o-carboxy or alkoxycarbonyl-substituted phenyl)-trans-4-guanidinomethylcyclohexanecarboxamide derivatives having antiulcer action.
But, it is not known that these compounds possess antihypertensive, and coronary or cerebral circulation-improving activities.